Cyclic urea derivatives as potent NK1 selective antagonists. Part II: Effects of fluoro and benzylic methyl substitutions

Shue, Ho‐Jane; Chen, Xiao; Schwerdt, John; Paliwal, Sunil; Blythin, David J.; Li, Gang; Gu, Danlin; Wang, Xiao-Bing; Reichard, Gregory A.; Wang, Hongwu; Piwinski, John J.; Duffy, Ruth A.; Lachowicz, Jean E.; Coffin, Vicki L.; Nomeir, Amin A.; Morgan, Cynthia A.; Varty, Geoffrey B.; Shih, Neng‐Yang

doi:10.1016/j.bmcl.2005.10.072

Cited by 28 publications

(14 citation statements)

References 11 publications

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“…To showcase the application of [Co(P1)]-catalyzed intramolecular aziridination of allylic sulfamoyl azides and the subsequent transformations of the resulting sulfonylated [3.1.0] bicyclic diaza aziridines for target synthesis,wedeveloped ac oncise and high-yielding synthetic route to the bioactive compound 13 (Scheme 5), [17] one member of af amily of potent Neurokinin 1( NK 1 )r eceptor antago-nists. [18] Thec ompound 13 consists of ac ore structure of N-methylimidazolidin-2-one with aquaternary carbon center bearing phenyl and (3,5-bis(trifluoromethyl)benzyloxy)methyl groups.S tarting from N-methyl-2-phenylallylamine, the allylic sulfamoyl azide 1o was readily prepared in 91 % yield.…”

Section: Angewandte Chemiementioning

confidence: 99%

Intramolecular Radical Aziridination of Allylic Sulfamoyl Azides by Cobalt(II)‐Based Metalloradical Catalysis: Effective Construction of Strained Heterobicyclic Structures

et al. 2016

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Co(II)-based metalloradical catalysis (MRC) has been successfully applied for effective construction of the highly strained 2-sulfonyl-1,3-diazabicyclo[3.1.0]-hexane structures in high yields through intramolecular radical aziridination of allylic sulfamoyl azides. The resulting [3.1.0]-bicyclic aziridines prove to be versatile synthons for preparation of a diverse range of 1,2- and 1,3-diamine derivatives by selective ring-opening reactions in exo- and endo-fashion, respectively. As a demonstration of its application for target synthesis, the metalloradical intramolecular aziridination reaction has been incorporated as a key step for efficient synthesis of a potent neurokinin 1 (NK1) antagonist in 60% overall yield.

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Section: Angewandte Chemiementioning

confidence: 99%

Intramolecular Radical Aziridination of Allylic Sulfamoyl Azides by Cobalt(II)‐Based Metalloradical Catalysis: Effective Construction of Strained Heterobicyclic Structures

et al. 2016

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“…To showcase the application of [Co(P1)]-catalyzed intramolecular aziridination of allylic sulfamoyl azides and the subsequent transformations of the resulting sulfonylated [3.1.0] bicyclic diaza aziridines for target synthesis,wedeveloped ac oncise and high-yielding synthetic route to the bioactive compound 13 (Scheme 5), [17] one member of af amily of potent Neurokinin 1( NK 1 )r eceptor antago- Angewandte Chemie Zuschriften nists. [18] Thec ompound 13 consists of ac ore structure of N-methylimidazolidin-2-one with aquaternary carbon center bearing phenyl and (3,5-bis(trifluoromethyl)benzyloxy)methyl groups.S tarting from N-methyl-2-phenylallylamine, the allylic sulfamoyl azide 1o was readily prepared in 91 % yield.…”

Section: Angewandte Chemiementioning

confidence: 99%

Intramolecular Radical Aziridination of Allylic Sulfamoyl Azides by Cobalt(II)‐Based Metalloradical Catalysis: Effective Construction of Strained Heterobicyclic Structures

et al. 2016

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Cobalt(II)-based metalloradical catalysis (MRC) has been successfully applied for effective construction of the highly strained 2-sulfonyl-1,3-diazabicyclo[3.1.0]hexane structures in high yields through intramolecular radical aziridination of allylic sulfamoyl azides.T he resulting [3.1.0] bicyclic aziridines prove to be versatile synthons for the preparation of adiverse range of 1,2-and 1,3-diamine derivatives by selective ring-opening reactions.A sademonstration of its application for target synthesis,t he metalloradical intramolecular aziridination reaction has been incorporated as akey step for efficient synthesis of ap otent neurokinin 1( NK 1 )a ntagonist in 60 % overall yield.Radical chemistry has displayed vast potential in modern organic synthesis as it has many attractive features which are complementary to ionic chemistry. [1] To address the existing challenges in the field, [2] metalloradical catalysis (MRC) presents anew approach to achieving controllable reactivities and selectivities through catalytic generation of metal-stabilized organic radicals,such as the fundamentally new a-Co IIIalkyl and a-Co III -aminyl radicals. [3,4] Forexample,the a-Co IIIaminyl radicals (also known as cobalt(III) nitrene radicals), which can be generated through au nique radical-transfer process from the cobalt-centered radicals of cobalt(II) porphyrins [Co(Por)] to organic azides upon metalloradical activation, [3e-g] have demonstrated controlled reactivities for both hydrogen atom abstraction of CÀHb onds and radical addition to C=Cb onds to furnish ac atalytic radical amination [5] and aziridination, [6] respectively,w ith high levels of selectivity.I np articular,t he cobalt(II)-based MRC system exhibits remarkable chemoselectivity,a se xemplified by the selective transformation of the sulfamoyl azide containing both N-allyl and N-bis(homoallyl) groups (Scheme 1A). Exclusive intramolecular 1,6-radical amination of the allylic CÀHbonds was reported and there was no observation of the potential intramolecular radical aziridination of the C=C bonds. [5e] In the absence of the more reactive N-bis(homoallyl) group,h owever,i tw as unclear if intramolecular aziridination of N-allyllic sulfamoyl azides was possible in view of the high strain associated with the resulting 2-sulfonyl-1,3-diazabicyclo[3.1.0]hexane structure (Scheme 1B). [7] This type of catalytic process (Scheme 1C)w ould require the corresponding a-Co III -aminyl radical A to undergo efficient intramolecular addition to the olefin unit to generate either the g-Co III -alkyl radical intermediate Ba (Scheme 1C;l eft: 5-exo-trig cyclization)o rt he g-Co III -alkyl radical Bb (Scheme 1C;r ight:6 -endo-trig cyclization), followed by 3-exo-tet radical cyclization to deliver the aziridine product with regeneration of the [Co(Por)] catalyst. If successful, this catalytic transformation would be highly useful as the resulting [3.1.0] heterobicyclic structures are the key motifs in compounds of medicinal importance,and can also serve as versatile building blocks ...

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“…The E-and Z-isomers are only differentiated by the 1 H NMR chemical shift of the oxime methyl ether function. 1 H NMR (400 MHz, CDCl 3 ): d = 4.78 (s, 3 H, NOMe, E-isomer), 4.72 (s, 0.3 H, NOMe, Z-isomer), 2.68 (tt, 1 H, J = 5.5 Hz,), 2.53 (t, 1 H, J = 5.5 Hz), 2.33-2.46 (m, 2 H), 2.03 (m, 1 H), 1.83-1.90 (m, 2 H), 1.32 (d, 1 H, J = 10.2 Hz), 1.24 (s, 3 H), 0.78 (s, 3 H). 13 C NMR (100 MHz, CDCl 3 ): d = 168.…”

Section: Experimental Section (+)-Nopinone Oxime Ethermentioning

confidence: 99%

“…The oxime ether function represents a great interest in organic synthesis as it can easily be converted into ketone, 1 amine, 2 or nitrile 3 derivatives. Moreover, this function shows an interesting reactivity in radical reactions 4 and 'enol-like' reactions 5 or can be used as efficient substrates in 1,2-addition reactions of organometallics reagents.…”

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confidence: 99%

Stereocontrolled α-Alkylation of Oxime Ether Derived from Terpene: Efficient Synthesis of New Chiral γ- and δ-Amino Alcohols

Jennequin¹,

Labat²,

Toupet³

et al. 2008

Synlett

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Cyclic urea derivatives as potent NK1 selective antagonists. Part II: Effects of fluoro and benzylic methyl substitutions

Cited by 28 publications

References 11 publications

Intramolecular Radical Aziridination of Allylic Sulfamoyl Azides by Cobalt(II)‐Based Metalloradical Catalysis: Effective Construction of Strained Heterobicyclic Structures

Intramolecular Radical Aziridination of Allylic Sulfamoyl Azides by Cobalt(II)‐Based Metalloradical Catalysis: Effective Construction of Strained Heterobicyclic Structures

Intramolecular Radical Aziridination of Allylic Sulfamoyl Azides by Cobalt(II)‐Based Metalloradical Catalysis: Effective Construction of Strained Heterobicyclic Structures

Stereocontrolled α-Alkylation of Oxime Ether Derived from Terpene: Efficient Synthesis of New Chiral γ- and δ-Amino Alcohols

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